Low testosterone is common in men with coronary heart disease and negatively impacts survival

A total of 930 men (mean age 61 years) were followed in a prospective cohort study for a mean of 6.9 years to determine the prevalence of testosterone deficiency and to investigate the effect of serum testosterone levels on survival in men with confirmed coronary disease.1 The cohort was a consecutive series of men referred to a tertiary cardiothoracic centre for diagnostic coronary angiography between June 2000 and June 2002. Significant coronary artery disease was defined as 70% or greater stenosis in any epicardial coronary artery or 50% or greater stenosis of the main stem of the left coronary artery.

Key Points

The nested case-control study showed:

20.9% of men had biochemical testosterone deficiency defined as bioavailable testosterone <2.6 nmol/L, 16.91% using testosterone <8.1 nmol/L and 24% using either1

There was excess mortality in testosterone-deficient men; 21% versus 12% in those with testosterone levels in the normal range (>2.6 nmol/L), p=0.002 (Figure 1)1

Low serum testosterone was one of only four variables found to influence the time to all-cause mortality in multivariate analysis (hazard ratio [HR] 2.27)1

The other variables significantly influencing time to all-cause mortality were presence of left ventricular dysfunction (HR 3.85), aspirin therapy (HR 0.63) and β-blocker therapy (HR 0.45)1

Low bioavailable testosterone more than doubled adjusted all-cause and vascular mortality (HR 2.2, p<0.0001 for all-cause mortality and HR 2.2, p=0.007 for vascular mortality) compared with those with normal levels of testosterone1

Overall, serum total testosterone was inversely associated with mortality (HR 0.96), with a baseline level of <15.1 nmol/L associated with an all-cause HR of 1.86 and vascular mortality with a HR of 2.5.1

What is known

The risk for men of dying from coronary disease is double that for women, even after controlling for cardiovascular risk factors.2 Although there has been an assumption that testosterone has harmful effects on the cardiovascular system, there is little evidence that endogenous testosterone increases cardiovascular risk and the role of testosterone status and testosterone replacement therapy on male health remains controversial.3It is well established that high doses of exogenous anabolic steroids have a deleterious effect on cardiac disease.4 However, high levels of endogenous testosterone within the normal range appear not to be detrimental, and there is increasing evidence that low testosterone levels in men are associated with increased cardiovascular risk resulting from a more adverse cardiometabolic profile.5,6 Furthermore, testosterone replacement therapy improves insulin resistance, glycaemic control, central obesity, lean body mass, hypercholesterolaemia and pro-inflammatory cytokines associated with diabetes, atherosclerosis and the metabolic syndrome.7-9

There is accumulating evidence that low testosterone levels are associated with an increase in all-cause and cardiovascular mortality.10-13 However, this study is the first to examine the effects of low testosterone in men with established cardiovascular disease.

What this study adds

This is the first epidemiological study to demonstrate that low testosterone is a marker of early mortality in men with vascular disease, who have been excluded in previous follow-up studies of testosterone. In an editorial accompanying the study, Drs Ronald Ma and Peter Tong note that the study contributes to the emerging picture suggesting that reduced testosterone levels in men may be associated with increased cardiovascular risk, and suggest that testosterone measurements may have a place in the evaluation of cardiovascular risk in male patients, although issues to be resolved include the variability of testosterone concentrations, the influence of acute or chronic concomitant illness, the accuracy and reliability of current assays and whether to measure sex-hormone binding globulin, total or free testosterone.14

This study shows that testosterone deficiency is common in patients with coronary disease and has a considerable negative impact on survival. The authors conclude that a prospective outcome trial of testosterone replacement on mortality in men with low testosterone is the next logical step, targeting high-risk populations such as men with cardiac disease or diabetes, who have the most to gain from the potentially beneficial effects.1

Figure 1: Excess mortality after a mean follow-up of 6.9 years in men with confirmed coronary disease and low serum testosterone levels.1